Marijuana is the most commonly used illicit drug in the United States. Although its use and potential health consequences are widespread and the basic science research on cannabinoids is well developed, little research has focused on the clinical treatment of marijuana use disorders. One area of importance in the study of substance use disorders is relapse. Several risk factors have been recognized as critical in the elicitation of craving and drug-seeking, such as exposure to drug-related cues or experiencing negative emotional stimuli. Although these factors have been explored in other substance use disorders, little research has focused on drug cue-related or stress- induced relapse in marijuana dependent individuals. The proposed R-21 project will investigate the effects of marijuana cues, stress and their interaction in a clinical laboratory paradigm. Specifically, HPA axis (ACTH, cortisol), physiologic (heart rate, blood pressure, skin conductance) and subjective responses to an acute stress (Trier Social Stress Test) or no stress condition followed by the presentation of marijuana- related cues will be investigated in marijuana-dependent individuals. It is predicted that stress exposure will potentiate the response to drug-related cues. This project is designed to extend our ongoing research in the area of cue- and stress-related reactivity in drug-dependent individuals to the area of marijuana dependence. Exploration of potential precipitants of relapse can have important implications for prevention and treatment of marijuana dependence. Marijuana is the most commonly used illicit drug, yet little is known about factors that may precipitate relapse to marijuana use. The interaction of stress and cues has not been systematically investigated although this paradigm closely mirrors real-life situations. Results from this novel study will address how stress impacts other relapse risk factors, and may help direct future treatment studies in which therapies are directed to reduce stress-potentiated craving to cues in marijuana-dependent individuals. [unreadable] [unreadable] [unreadable]